Mirvetuximab soravtansine shows durable efficacy in ovarian cancer subset
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Folate receptor alpha expression predicted benefit from mirvetuximab soravtansine in platinum-resistant high-grade serous epithelial ovarian, primary peritoneal or fallopian tube cancers, according to a results of the phase 3 SORAYA study.
The findings, presented during Society of Gynecologic Oncology 2022 Annual Meeting on Women’s Cancer, showed mirvetuximab soravtansine (IMGN853, ImmunoGen), an antibody-drug conjugate, induced clinically meaningful and durable antitumor activity with acceptable tolerability among the subgroup of women, who have limited treatment options.
“In the platinum-resistant setting and particularly in later-line treated patients, response rates with available therapy are in the single digits with significant toxicities,” Ursula A. Matulonis, MD, chief of the division of gynecologic oncology at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, said in a press release from Dana-Farber. “These data have the potential to be transformative for ovarian cancer patients and their physicians.”
Background and methodology
Matulonis and colleagues wrote that single-agent chemotherapies for treatment of platinum-resistant ovarian cancer have limited clinical activity and considerable toxicity. The folate receptor is an attractive target for cancer drugs because it is much more abundant in certain tumor cells compared with normal cells, according to the researchers. Mirvetuximab soravtansine connects a folate receptor alpha-binding antibody on high-grade serous ovarian cancers with maytansinoid DM4 (a potent tubulin-targeting agent).
The researchers evaluated the agent among 106 women with platinum-resistant, high-grade, serous ovarian cancer that highly expressed folate receptor alpha who received one to three prior therapies, including bevacizumab (Avastin, Genentech); 51% received three prior lines of therapy and 48% received a prior poly(ADP-ribose) polymerase (PARP) inhibitor.
Researchers administered mirvetuximab soravtansine dosed at 6 mg/kg adjusted ideal body weight via IV on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. Confirmed objective response rate per RECIST version 1.1 by investigator served as the primary endpoint; secondary endpoints included safety and tolerability.
Key findings
At median follow-up of 8.5 months by the Nov. 16 data cutoff, Matulonis and colleagues reported objective responses in 34 of 105 efficacy evaluable patients, for an investigator-assessed ORR of 32.4% (95% CI, 23.6-42.2), including five complete responses. Blinded, independent central review reported an ORR of 31.6% (95% CI, 22.4-41.9%), including five complete responses.
Researchers observed a duration of response of 5.9 months (95% CI, 5.6-7.7). Additionally, they reported duration of response continued to evolve, with 15 responders remaining on mirvetuximab soravtansine at data cutoff.
Investigator-assessed ORRs among subgroups included:
- 35.3% (95% CI, 22.4-49.9) among patients with one or two prior therapies;
- 30.2% (95% CI, 18.3-44.3) among patients with three prior therapies;
- 38% (95% CI, 24.7-52.8) among patients who received prior PARP inhibitor treatment; and 27.5% (95% CI, 15.9-41.7) among patients who had not received prior PARP inhibitors.
Researchers called the mirvetuximab soravtansine treatment well tolerated; only one patient discontinued treatment due to an ocular event. Treatment-related adverse events led to dose reductions for 19% of patients, dose delays for 32% of patients and discontinuation among 7% of patients. Common treatment-related adverse events, mostly low grade and generally reversible, included blurred vision (41% all grade; 6% grade 3 or higher), keratopathy (36% all grade; 8% grade 3 or higher) and nausea (29% all grade; 0% grade 3 or higher).
Implications
In a press release issued by ImmunoGen, Matulonis said the treatment could become practice changing for women with platinum-resistant ovarian cancer who have limited treatment options.
“With an objective response rate of 32.4% — far exceeding that seen with current therapies — and a median duration of response approaching 7 months, mirvetuximab continues to demonstrate impressive efficacy in patients with platinum-resistant disease who have already received bevacizumab,” Matulonis said. “The antitumor activity and consistent safety and tolerability data from the SORAYA trial further underscore the potential of mirvetuximab, if approved, to become a practice-changing, biomarker-driven standard of care for these patients.”
References:
Matulonis UA, et al. Abstract LB4. Presented at Society of Gynecologic Oncology 2022 Annual Meeting on Women's Cancer. March 18-21, 2022.
ImmunoGen presents full results from positive pivotal SORAYA trial of mirvetuximab soravtansine in ovarian cancer at SGO Annual Meeting. https://investor.immunogen.com/news-releases/news-release-details/immunogen-presents-full-results-positive-pivotal-soraya-trial. Published March 19, 2022. Accessed March 21, 2022.
Conjugate therapy produces remissions in one-third of patients with drug-resistant ovarian cancer, study results show. https://www.dana-farber.org/newsroom/news-releases/2022/conjugate-therapy-produces-remissions-in-one-third-of-patients-with-drug-resistant-ovarian-cancer--study-results-show/. Published March 19, 2022. Accessed March 21, 2022.
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Matulonis UA, et al. Abstract LB4. Presented at Society of Gynecologic Oncology 2022 Annual Meeting on Women's Cancer. March 18-21, 2022.
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